Many epidemiological studies have shown that hypercholesterolemia, hypertension and smoking comprise the three major risk factors for arteriosclerotic diseases, such as myocardial infarction, angina pectoris and cerebral infarction. Appropriate control of blood cholesterol level is therefore critical to the prevention or treatment of arteriosclerotic diseases, such as ischemic heart diseases. Among the drugs that decrease the blood cholesterol level are drugs that capture bile acid and inhibit its absorption, such as cholestyramine and colestipol (disclosed in U.S. Pat. No. 4,027,009, for instance) and drugs that inhibit acyl coenzyme A cholesterol acyl transferase (ACAT) and suppresses intestinal absorption of cholesterol, such as melinamide (disclosed in British Patent No. 1123004), as well as drugs that suppress cholesterol biosynthesis, which have drawn attention. Cholesterol biosynthesis suppressors in pharmaceutical use include lovastatin (disclosed in U.S. Pat. No. 4,231,938), simvastatin (disclosed in U.S. Pat. Nos. 4,231,938 and 4,444,784) and pravastatin (disclosed in U.S. Pat. No. 4,346,227), all inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. When HMG-COA reductase is inhibited, however, not only cholesterogenesis, but also biosynthesis of other components essential to be alive, such as ubiquinone, dolichol and heme A, are inhibited, resulting in adverse effects of concern. Ubiquinone, dolichol, heme A etc. are known to be biosynthesized from farnesyl pyrophosphate in the cholesterol biosynthesis pathway; to prevent adverse effects due to their reduction, it is desirable that the enzymes after farnesyl pyrophosphate in the cholesterogenesis are inhibited. For example, 2,3-oxidosqualene cyclase (EC 5.4.99.7) is an enzyme that converts 2,3-oxidosqualene to lanosterol; 2,3-oxidosqualene cyclase inhibition results in a diminishment of cholesterol synthesis, owing to inhibited production of lanosterol, which is used for conversion to cholesterol, eventually leading to lower blood cholesterol levels. Also, the 2,3-oxidosqualene accumulation, as a result of 2,3-oxidosqualene cyclase inhibition, is metabolically converted to oxysterol via dioxide squalene, which is known as an HMG-COA reductase repressor [F. R. Taylor et al., Journal of Biological Chemistry, 1986, vol. 261 (32), pp. 15039-15044]. 2,3-Oxidosqualene cyclase inhibitors are therefore capable of inhibiting cholesterogenesis potently by the synergetic effect of HMG-COA reductase suppression at the transcription level, in addition to the inhibition of one enzyme after farnesyl pyrophosphate in the cholesterogenesis pathway. Already reported 2,3-oxidosqualene cyclase inhibitors include diphenyl derivatives (disclosed in European Patent No. 464465), aminoalkoxybenzene derivatives (disclosed in European Patent No. 410359), piperidine derivatives (described by D. S. Dodd et al. in the Journal of Organic Chemistry, 1992, vol. 57, pp. 2794-2803 and 7226-7234; Japanese Patent Unexamined Publication No. 234362/1992), decalin derivatives, azadecalin derivatives and indane derivatives [described in WO 80/08450; Journal of Biological Chemistry, 1981, vol. 254, pp. 11258-11263; N. Gerst et al., Biochemical Pharmacology, 1988, vol. 37, pp. 1955-1964; M. W. Wannamaker, Journal of Medicinal Chemistry, 1992, vol. 35, pp. 3581-3583; Japanese Patent Unexamined Publication Nos. 140112/1993 and 3144/1989], 2-aza-2,3-dihydrosqualene and 2,3-epiminosqualene [described by A. Duriatti et al. in Biochemical Pharmacology, 1985, vol. 34, pp. 2765-2777], squalenoid epoxide vinyl ether [described by M. Ceruti et al. in the Journal of the Chemical Society, Perkin Transaction 1, 1988, pp. 461-469], 29-methyliden-2,3-oxidosqualene [described in the Journal of American Chemical Society, 1991, vol. 113, pp. 9673-9674], azacycloalkane derivatives (disclosed in Japanese Patent Unexamined Publication No. 192256/1994) and arylcycloalkylamine derivatives (Japanese Patent Unexamined Publication No. 211763/1994). As concerns infectious diseases, the sterol biosynthesized by fungi is ergosterol, while that by mammals is cholesterol; however, since the process of biosynthesis to lanosterol is common between the two kinds of sterol, inhibition of the process at a point before lanosterol suppresses the synthesis of both. 2,3-Oxidosqualene cyclase inhibitors are therefore expected to exhibit antifungal action [J. L. Adams et al., Comprehensive Medicinal Chemistry, 1990, vol. 2, pp. 333-364].
Compounds that inhibit cholesterol biosynthesis are useful in the treatment of some syndromes, especially hypercholesterolemia and hyperlipidemia, which comprise risk factors for onset of atherosclerotic vascular lesions and diseases subsequent thereto, such as coronary artery disease (CHD), cerebral ischemia, intermittent claudication and necrosis. Major symptoms of atherosclerosis are intimal proliferation of macrophages and vascular smooth muscle cells, and cholesterol accumulation in such cells. It is a well-known that hypercholesterolemia, especially increased low-density lipoprotein (LDL)-cholesterol, is an important risk factor in the development of atherosclerosis. Since epidemiological studies have revealed that the incidence of coronary heart disease can be decreased by lowering blood cholesterol [see Lipidology 2(4), 234, 1991], blood lipid-lowering agents have been used to suppress atherosclerotic vascular lesions. Such use, however, is for prophylaxis, rather than treatment.
It is also known epidemiologically that high-density lipoprotein (HDL)-cholesterol lowers the incidence of heart disease. Regarding the mechanism of this action, HDL is known to reduce cholesterol from foam cells. However, there is no report regarding substances used to increase blood HDL or HDL-cholesterol.
Japanese Patent Unexamined Publication No. 41332/1979 describes as a sickle cell anemia or sicklemia remedy, possessing anti-inflammatory, vasodilating and platelet aggregation-inhibiting activities, a compound represented by the formula: ##STR1## wherein x represents an atom of oxygen or sulfur; R represents a group selected from the group consisting of hydrogen atom; phenyl group; phenyl groups substituted by at least one substituent selected from the group consisting of halogen atoms, lower alkyl, lower alkoxy, nitro, amino, sulfonylamino, aryl, carboxy, alkoxycarbonyl, cyano, hydroxymethyl and methylenedioxy groups; styryl, naphthyl, thienyl and benzhydryl groups, each of which may be substituted by at least one substituent selected from the group consisting of halogen atoms, lower alkyl, lower alkoxy, aryl, nitro, amino, sulfonylamino, carboxy, alkoxycarbonyl, cyano, hydroxymethyl and methylenedioxy groups; benzoyl group; and benzoyl groups substituted by at least one substituent selected from the group consisting of halogen atoms, lower alkyl, lower alkoxy, nitro, amino and sulfonylamino groups; R.sup.1 and R.sup.2 independently represent at least one atom or group selected from the group consisting of hydrogen atom, halogen atoms, hydroxy, lower alkyl, lower alkoxy, nitro and amino groups; R.sup.3 represents a group selected from the group consisting of hydrogen atom, halogen atoms, hydroxy, lower alkyl, lower alkoxy, nitro and amino groups; n represents an integer from 0 to 15; when n is greater than 1, the R.sup.3 radicals in the respective CHR.sup.3 groups may have different meanings. PCT International Patent Application WO93/13105 describes as an antipsychotic or antianxiety drug a compound represented by the formula: ##STR2## wherein ring S is a thiophene ring; R.sup.1 represents a hydrogen atom, a halogen, an alkyl, or the like; R.sup.2 represents a hydrogen atom, an alkyl, an acyl, or the like; G represents --CH.sub.2 --, --CH(OH)--, --CO--, or the like; Q represents an alkylene; T represents --NH.sub.2, --NHRa (Ra represents an alkyl, a cycloalkyl, or the like), or --N(Rb)(Rc) (Rb and Rc independently represent an alkyl, or the like, or bind together to form a cyclic amino); D represents --CH.sub.2 -- or --S--; A and B independently represent a carbonyl or thiocarbonyl, or none; m and n each represent an integer from 0 to 4, but m+n does not exceed 4, exemplified in Example 41 by a compound represented by the formula: ##STR3##
However, no compounds have been found that are fully satisfactory in 2,3-oxidosqualene cyclase-inhibiting and blood cholesterol-lowering activities; there is need for the development of such compounds.